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The case report shows the safety and efficacy of insulin treatment with Advanced Hybrid Closed Loop (AHCL) system in a young patient affected by permanent neonatal diabetes mellitus (PNDM) due to chromosome 8 deletion syndrome involving the GATA4 gene. In the first days of life, he presented hyperglycaemia and started an intravenous insulin infusion therapy, replaced by a continuous subcutaneous insulin infusion (CSII) with Medtronic Minimed 780G® insulin pump (Medtronic, Northridge, CA, USA). At the age of 2 years, the off-label activation of SmartGuard® automated insulin delivery mode led to a great improvement in glycaemic control, reaching all recommended targets. At the 1-month follow-up visit, Time in Range (TIR) increased from 66% to 79%, with a Time in Tight Range (TTIR) of 55% and a reduction of 11% in time in hyperglycaemia and of 2% in time in hypoglycaemia. During the entire follow-up, no episodes of ketoacidosis or severe hypoglycaemia were observed and the patient maintained the glycaemic recommended targets reached at 1 month. Maintaining optimal glycaemic control and reducing hyperglycaemia are essential for brain growth and neurocognitive development in young patients. AHCL use should be considered to ensure good glycaemic control in patients affected by neonatal diabetes.

Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. Clinical signs of rickets are related to the age of the patient, the duration of the disease, and the underlying disorder. The most common signs of rickets are swelling of the wrists, knees or ankles, bowing of the legs (knock-knees, outward bowing, or both) and inability to walk. However, clinical features alone cannot differentiate between the various forms of rickets. Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. This position paper reviews the relevant literature and presents the expertise of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP). The aim of this document is to provide practical guidance to specialists and healthcare professionals on the main criteria for diagnosis, treatment, and management of patients with rickets. The various forms of rickets are discussed, and detailed references for the discussion of each form are provided. Algorithms to guide the diagnostic approach and recommendations to manage patients with rare forms of hereditary rickets are proposed.

Objective: This Italian survey aims to evaluate real-life long-term efficac y and safety of recombinant human growth hormone (rhGH) therapy in children wit h short stature homeobox-containing gene deficiency disorders (SHOX-D) and to id entify potential predictive factors influencing response to rhGH therapy. Design and methods: This is a national retrospective observational study collectin g anamnestic, anthropometric, clinical, instrumental and therapeutic data in children and adolescents with a genetic confirmation of SHOX-D treated on rhG H. Data were collected at the beginning of rhGH therapy (T0), yearly during the first 4 years of rhGH therapy (T1, T2, T3 and T4) and at near-final height (nFH) (T5), when availab le. Results: One hundred and seventeen SHOX-D children started rhGH therapy (initial dose 0.23 ± 0.04 mg/kg/week) at a mean age of 8.67 ± 3.33 years (74% prepubertal), 99 completed the first year of treatment and 46 reached nFH. During rhGH therapy, growth velocity (GV), standard deviation score (SDS) and height (H) SD S improved significantly. Mean H SDS gain from T0 was +1.14 ± 0.58 at T4 and +0.80 ± 0.98 at T5. Both patients carrying mutations involving intragenic SHOX region (group A) a nd ones with regulatory region defects (group B) experienced a similar beneficial therap eutic effect. The multiple regression analysis identified the age at the start of rhGH trea tment (β = −0.31, P = 0.030) and the GV during the first year of rhGH treatment ( β = 0.45, P = 0.008) as main independent predictor factors of height gain. During rhGH thera py, no adverse event of concern was reported. Conclusions: Our data confirm the efficacy and safety of rhGH therapy in SHOX- D children, regardless the wide variety of genotype. Significance Statement: Among children with idiopathic short stature, the prevalence o f SHOX-D is near to 1/1000–2000 (1.1–15%) with a wide phenotypic spectrum. Current guidelines support rhGH therapy in SHOX-D children, but long-te rm data are still few. Our real-life data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless of the wide variety of genotypes. Moreover, rhGH the rapy seems to blunt the SHOX-D phenotype. The response to rhGH in the first year of trea tment and the age when rhGH was started significantly impact the height gain.

Abstract Background SHOX enhancer CNVs, affecting one or more of the seven recognized evolutionary conserved non‐coding elements (CNEs) represent one of the most frequent cause of SHOX‐haploinsufficiency. During the diagnostic workflow deletions/duplications have been identified downstream SHOX not including any of the these CNEs. Methods Fine tiling aCGH and breakpoint PCR were used to characterize the critical interval and to search for novel alterations in a cohort of selected patients. Results Screening of 252 controls provided evidence that duplications in this area represent likely benign variants whereas none of the deletions were detected. These findings suggested that other alterations relevant for SHOX‐haploinsufficiency might be missed by the standard diagnostic methods. To identify such undisclosed elements, the aCGH was used to reanalyze 52 unresolved cases with clinical features strongly suggestive of SHOX‐haploinsufficiency. This analysis followed by the screening of 210 patients detected two partially overlapping small deletions of ~12 and ~8 kb in four unrelated individuals, approximately 15 kb downstream SHOX, that were absent in 720 normal stature individuals. Conclusion Our results strengthen the hypothesis that alterations of yet unidentified cis‐regulatory elements residing outside those investigated through conventional methods, might explain the phenotype in ISS/LWD patients thus enlarging the spectrum of variants contributing to SHOX‐haploinsufficiency.

The ageing of population is a phenomenon that is affecting the majority of developed countries around the world and will soon affect developing economies too. In recent years, both industry and academia are focused on the development of several solutions aimed to guarantee a healthy and safe lifestyle to the elderly. In this context, the behavioral analysis of elderly people can help to prevent the occurrence of Mild Cognitive Impairment (MCI) and frailty problems. The innovative technologies enabling the Internet of Things (IoT) can be used in order to capture personal data for automatically recognizing changes in elderly people behavior in an unobtrusive, low-cost and low-power modality. This work aims to describe the ongoing activities within the City4Age project, funded by the Horizon 2020 Programme of the European Commission, mainly focused on the use of IoT technologies to develop an innovative AAL system able to capture personal data of elderly people in their home and city environments. The proposed architecture has been validated through a proof-of-concept focused mainly on localization issues, collection of ambient parameters, and user-environment interaction aspects.

The analysis of locomotion in laboratory animals plays a crucial role in many scientific research areas. In fact, important information on animals’ behavior and their reaction to a particular stimulus is deduced from a careful analysis of their movements. The techniques commonly adopted to support such analysis have many limitations, which make the related systems particularly ineffective. On the one hand, the human observation and annotation process is strongly observer-dependent and expensive in terms of time and efforts. On the other hand, the use of more sophisticated systems based on video recordings and recognition algorithms is very expensive and complex. In order to face this challenge, this paper presents a tracking solution based on passive Radio Frequency Identification (RFID) technology in Ultra High Frequency (UHF) band, allowing the tracking of laboratory animals with a high accuracy. The overall solution consists of a hybrid system including hardware and software components. In particular, in this paper, the attention is focused on the software component as the hardware has already been described in previous works. The software component is a Web-oriented solution that offers a complete 2D and 3D information tool including reports, dashboards, and tracking graphs. The proposed solution was widely tested using twelve laboratory mice and compared with an automated video-tracking software (i.e., EthoVision) in order to demonstrate its effectiveness and reliability. The obtained results have demonstrated that the proposed solution is able to correctly detect and reconstruct the events occurring in the animals’ cage, and to offer a complete and user-friendly tool to support researchers in behavioral analysis of small laboratory animals.